Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Squamous Cell Carcinoma of the Head and Neck, Head and Neck Cancer, PI3K-δ,γ, PI3K Inhibitor
Brief summary
This study was designed to assess the safety and preliminary efficacy of duvelisib in combination with pembrolizumab in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Detailed description
This was a non-randomized, open-label Phase 1b/2 study designed to evaluate safety, tolerability, and preliminary efficacy of duvelisib in combination with pembrolizumab in participants with R/M HNSCC who were eligible for pembrolizumab monotherapy based on the current pembrolizumab prescribing information.
Interventions
DRUGDuvelisib
Phosphoinositide 3-kinase (PI3K) Inhibitor
BIOLOGICALPembrolizumab
Immunotherapy (programmed cell death protein 1 \[PD-1\] inhibitor)
Sponsors
SecuraBio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group performance status ≤ 1 * Histologically or cytologically confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that was considered incurable by local therapies * Eligible for pembrolizumab monotherapy based on the current prescribing information for pembrolizumab (Keytruda 2019) * Must have had 0 to 2 prior therapies for R/M HNSCC * At least 1 measurable lesion (which has not been previously irradiated) according to Response Evaluation Criteria in Solid Tumors version 1.1 * For stage 1 only: Must have had at least 1 other lesion that could be biopsied and willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion * For stage 1 only: Must have been willing to undergo a pretreatment and on-treatment biopsy of the available tumor lesion * Adequate organ function defined by the following laboratory parameters: * Absolute neutrophil count ≥ 1.5 × 10\^9/liter (L) * Platelet count ≥ 100 × 10\^9/L * Hemoglobin level ≥ 9.0 grams/deciliter (dL) * A serum creatinine level \< 1.5 milligrams/dL, or * Estimated creatinine clearance value ≥ 60 milliliters/minute (as determined by the Cockcroft-Gault method) for participants with creatinine levels \> 1.5 × institutional upper limit of normal (ULN) * Total bilirubin level ≤ 1.5 × ULN (exception: participants with Gilbert's Syndrome may have a bilirubin level \> 1.5 × ULN) * Aspartate aminotransaminase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum pyruvic transaminase levels ≤ 2.5 × ULN or ≤ 5 × ULN in participants with liver metastases * International normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, unless participant was receiving anticoagulant therapy in which case PT or aPTT must have been within therapeutic range of intended use of anticoagulants
Exclusion criteria
* Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease * Received anticancer treatment, major surgery, or any investigational drug within 30 days or 5 half-lives, whichever is shorter, before the start of study intervention * Received radiation therapy within 14 days before the start of study intervention, including, in addition (if necessary), the timeframe for resolution of any actual or anticipated toxicities from such radiation; Palliative radiation is allowed if \> 7 days and any toxicity is ≤ Grade 1 * Previous treatment with a PI3K, PD-1 or programmed cell death ligand 1 inhibitor * Have received organ or allogenic bone marrow or peripheral blood stem cell transplant * History of drug-induced colitis or drug-induced pneumonitis; history or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function; tuberculosis treatment within 2 years prior to the start of study intervention; chronic liver disease or veno-occlusive disease/sinusoidal obstruction syndrome * Active cytomegalovirus or Epstein-Barr virus infection; history of or known human immunodeficiency virus infection * Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection * Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening * Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A. No prior use within 2 weeks before the start of study intervention Received a live or live attenuated vaccine within 6 weeks of first dose of duvelisib * Unable to receive prophylactic treatment for pneumocystis, HSV, or VZV at screening * Any active gastrointestinal dysfunction interfering with the participant's ability to be administered oral medications * Known active central nervous system metastases and/or carcinomatous meningitis * QT interval \> 500 milliseconds (except for participants with a right or left bundle branch block) * New York Heart Association Class III or IV congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Number of Participants With Dose-limiting Toxicities | 4 weeks or 28 days | — |
| Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 months | Number of participants with TEAEs as assessed by the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) as a measure of safety and tolerability of duvelisib in combination with pembrolizumab. |
| Stage 1 and 2: Overall Response Rate (ORR) | Up to 2 years | Proportion of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 and 2: Overall Survival | From start of treatment until death (up to 2.5 years) | Time from start of treatment to death. |
| Stage 1 and 2: Maximum Observed Concentration [Cmax] | Up to 5 cycles (46 weeks) | Pharmacokinetics (PK) parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and Population PK (POPPK) modeling. |
| Stage 1: ORR | Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years) | Proportion of participants achieving complete CR or PR according to RECIST v 1.1. |
| Stage 1 and 2: Number of Participants With TEAEs | 24 months | Number of participants with TEAEs as assessed by CTCAE v5.0. |
| Stage 1 and 2: Area Under the Curve [AUC] | Up to 5 cycles (46 weeks) | PK parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and POPPK modeling. |
| Stage 1 and 2: Duration of Response (DOR) | From first response until documented PD (up to 2 years) | Time from response ≥ PR to documented disease progression according to RECIST v 1.1. |
| Stage 1 and 2: Progression-free Survival (PFS) | From start of treatment until documented PD or death (up to 2.5 years) | Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause. |
Countries
United States
Participant flow
Pre-assignment details
The study was terminated by the Sponsor due to low enrollment. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib + Pembrolizumab Stage 1: Duvelisib BID for 1 week followed by combination therapy with duvelisib BID + pembrolizumab q3w (Cycle 1 was 4 weeks consisting of the 1-week duvelisib monotherapy lead-in period followed by 1 dose of pembrolizumab in combination with 3 additional weeks of continuous dosing of duvelisib; subsequent cycles were 3 weeks).
Stage 2: Duvelisib BID + pembrolizumab q3w in 3-week cycles. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Stage 1 and 2: Overall Response Rate (ORR)
Proportion of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1).
Time frame: Up to 2 years
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Primary
Stage 1: Number of Participants With Dose-limiting Toxicities
Time frame: 4 weeks or 28 days
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Primary
Stage 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with TEAEs as assessed by the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) as a measure of safety and tolerability of duvelisib in combination with pembrolizumab.
Time frame: 6 months
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Area Under the Curve [AUC]
PK parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and POPPK modeling.
Time frame: Up to 5 cycles (46 weeks)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Duration of Response (DOR)
Time from response ≥ PR to documented disease progression according to RECIST v 1.1.
Time frame: From first response until documented PD (up to 2 years)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Maximum Observed Concentration [Cmax]
Pharmacokinetics (PK) parameters for duvelisib (and metabolite IPI-656) determined using bioanalytical data and Population PK (POPPK) modeling.
Time frame: Up to 5 cycles (46 weeks)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Number of Participants With TEAEs
Number of participants with TEAEs as assessed by CTCAE v5.0.
Time frame: 24 months
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Overall Survival
Time from start of treatment to death.
Time frame: From start of treatment until death (up to 2.5 years)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1 and 2: Progression-free Survival (PFS)
Time from start of treatment to documented disease progression according to RECIST v 1.1, or death due to any cause.
Time frame: From start of treatment until documented PD or death (up to 2.5 years)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Stage 1: ORR
Proportion of participants achieving complete CR or PR according to RECIST v 1.1.
Time frame: Until documented progressive disease (PD), unacceptable toxicity, discontinuation criteria are met, withdrawal, or death (up to 2 years)
Population: This study was terminated by the Sponsor. Due to study termination and only 2 participants receiving treatment, there are concerns regarding participant confidentiality, therefore no data are being reported.